PROJECT SUMMARY CANDIDATE: Christopher R. Martens, Ph.D., is a postdoctoral fellow in Integrative Physiology at the University of Colorado Boulder. In this K01 application, Dr. Martens aims to study the efficacy of a novel NAD+ boosting and calorie restriction-mimetic compound, nicotinamide riboside (NR), for improving memory and cerebrovascular function in older adults with amnestic mild cognitive impairment (aMCI). His immediate goal is to acquire the research training and professional skills necessary to transition from a postdoctoral fellow to an independent academic investigator. His long-term goal is to establish his own extramurally funded research program, with a primary focus on identifying therapeutic strategies for treating cerebrovascular dysfunction, improving cognitive function and reducing the risk Alzheimer's disease (AD) in older adults. CAREER DEVELOPMENT PLAN: Dr. Martens proposes to enhance his career development by: 1) acquiring new experimental skills in the assessment of cognitive and cerebrovascular function to support his proposed research plan; 2) receiving further training in MCI and AD pathophysiology, geriatrics and biostatistics; and 3) refining his professional skills development including formal course work, attendance and presentations at weekly journal clubs, university seminars, national scientific meetings, and Neurology and Geriatric Grand Round Series, and through regular interactions with his mentoring team. ENVIRONMENT: Dr. Martens will train in an outstanding environment supported by a multi-disciplinary team of mentors who will provide him with research and career development training. The principal mentor, Dr. Seals, is an internationally recognized and NIA-funded scientist with a strong record of successful mentoring in biomedical research pertaining to aging and vascular dysfunction. Co-Mentor Dr. Hughson is a leading expert in the assessment of cerebrovascular function and brain aging, and Dr. Bettcher is has extensive experience assessing cognitive function in patients with MCI. Dr. McQueen is director of biostatistics at the CU-Boulder Clinical and Translational Research Center (CTRC) and has extensive experience providing mentoring and consulting to trainees and faculty members conducting clinical trials. Co-mentors Dr. Potter and Dr. Schwartz are senior NIA investigators with expertise in Alzheimer's disease and geriatric medicine, respectively, and will provide mentorship to complement the research training & objectives. The mentorship team will provide specific expertise in key areas of the proposed research project and overall training plan. RESEARCH: aMCI is the earliest symptomatic stage in the development of AD, which is among the fastest growing causes of death in the US. aMCI is associated with impaired cerebrovascular function, which likely contributes to cognitive impairment and leads to increased risk of AD-related dementia. The proposed research seeks to test the efficacy a novel CR-mimicking dietary supplement, NR, for improving memory and cerebrovascular function in older adults with aMCI. Results from this study will provide insight into the efficacy of a potential beneficial therapy for preventing or delaying AD.